1. Field of the Invention
This invention relates to systems for performing hematological tests and, more particularly, to a system for measuring the coagulation time of plasma or whole blood by measuring the ultrasound backscattering characteristics of the plasma or whole blood.
2. Description of the Prior Art
Blood, when drawn from the blood vessels of a living body, is perfectly fluid. In a short time, it becomes viscid, and this viscidity increases rapidly until the whole mass of blood forms a clot. The essential substances in the blood necessary for this phenomena to occur are: (1) prothrombin, (2) calcium salts, (3) fibrinogen, and (4) tissue extract. The first three substances are in solution in the blood plasma. Tissue extract is set free by crushed tissue cells. Prothrombin may be converted to active thrombin by the action of calcium, but in the circulating blood, this is prevented by antithrombins. These antithrombins must first be neutralized by the tissue extract. Then the calcium reacts with the prothrombin to form thrombin, which, in turn, reacts with the fibrinogen to form fibrin. Initially, a fibrin monomer is formed, but subsequently the fibrin polymerizes to form a clot. The length of time required for the coagulation process is a function of the chemical characteristics of the blood sample. The concentration of fibrinogen in a sample of plasma or whole blood may be measured by adding a predetermined quantity of thrombin to the plasma and recording the time required for the fibrinogen to be converted to fibrin and form a clot. In the conventional thrombin time test, 0.2 ml of a solution of citrated plasma is mixed with 0.1 ml of thrombin solution at 37.degree. C. For normal plasma samples, a fibrin clot is formed in 15 to 20 seconds. However, the thrombin time is prolonged by traces of antithrombins, such as heparin, by pathological fibrinogens, by the presence of fibrin degradation products as a consequence of increased fibrinolysis, and by very low or very high fibrinogen concentrations in the plasma. The measurement of thrombin time is, therefore, a simple, but highly significant clinical assay.
Presently, the detection of a fibrin clot is based on two principles. One principle utilizes the lower electrical conductivity of fibrin with respect to fibrinogen. The plasma containing the fibrinogen is collected in a vibrating electrode which measures its conductivity. A marked decrease in the conductivity indicates that a fibrin clot has formed. A significant disadvantage of this method as conventionally practiced is that whole blood may not be used. Instead, it is first necessary to centrifuge the blood to separate the plasma therefrom.
The other principle for measuring the thrombin time makes use of the change in the optical absorption during the coagulation process. Fibrin has a higher coefficient of absorption than fibrinogen. Thus the transmission of light decreases during the coagulation process when fibrinogen is converted to fibrin by the addition of thrombin. As with the conductivity principle, this method for measuring the thrombin time must be performed with plasma since whole blood is too opaque and does not provide enough transmission. Thus the whole blood must first be centrifuged to obtain the plasma. The centrifuging necessary to perform thrombin time tests using present methods increases the cost of determining the thrombin time for a sample of blood and increases the time required to obtain the results of the test.
Recent technological developments in the field of medicine have greatly improved the available medical care. At the same time, the extensive use of procedures and instrumentation that have stemmed from these developments has added significantly to the cost of medical care. Therefore, there is considerable interest in procedures and methods for automating and reducing the cost of medical care. In particular, ultrasound is now extensively used in medicine. Therapeutical devices, such as heat generators, Doppler-flow meters and imaging systems, are a few examples of such uses. However, ultrasound has not yet been used in the hematological laboratory.